We have been studying means of active immunization against the human cytomegalovirus (CMV). A live attenuated vaccine, called Towne, was developed in this laboratory. Vaccination studies have been carried out in normal subjects and in renal transplant patients showing that Towne is well-tolerated, does not induce latency, and provides protection approximately equal to that of natural immunity. One objective is to find a means to prevent intrauterine CMV infection. We now propose to study vaccine efficacy in a population of normal women at high risk of infection, in order to determine whether vaccine can prevent infection by natural contact with CMV infected secretions. Since children in day care centers are frequently infected with CMV, their mothers and day care personnel are at risk of inopportune infection. We will give vaccine or placebo to seronegative female day care center personnel who are practicing contraception, comparing the two groups for CMV infection rates. We will subsequently vaccinate seronegative mothers who are on contraception, in order to compare them with placebo vaccinated mothers with respect to infection by CMV as a result of exposure to their day care center children. Infection will be determined by virus isolation from urine and the appearance of IgM antibodies. In order to develop new improved vaccines, we will study isolated CMV proteins. We have previously found that viral envelope can elicit neutralizing antibodies and CMV-specific lymphocyte proliferation in guinea pigs and in humans. gA, a particular glycoprotein complex contained in the envelope, can elicit the same responses in guinea pigs. Purified native gA will be used for immunization of humans, with determination of both humoral and cellular responses by a variety of methods. Immune responses to whole virus, early antigens and late antigens will be studied by radioimmunoprecipitation, immunoblot and lymphocyte proliferation in individual recipients of live vaccine, wild virus, and subunit vaccine to determine whether response to specific proteins correlate with neutralizing antibodies and with protection against infection or disease.